Multiple Somatic Mutations for Clonal Hematopoiesis Are Associated With Increased Mortality in Patients With Chronic Heart Failure

摘要

Clonal hematopoiesis of indeterminate potential (CHIP) is defined as a clonal outgrowth of hematopoietic cells with mutations in a restricted set of cancer driver genes in patients without frank malignancy. By definition, CHIP is defined by a variant allele frequency (VAF) of any mutation of at least 2%, although high-sensitivity sequencing approaches revealed the presence of smaller blood clones in 95% of healthy individuals.1 It was shown recently that patients with CHIP display a significantly increased mortality risk, which can be attributed to cardiovascular complications, namely ischemic stroke and coronary artery disease.2 We showed that mutations in the most common CHIP driver genes DNMT3A and TET2 associate with worse prognosis in patients with chronic heart failure.3 However, the impact of CHIP-mutations other than DNMT3A and TET2 on chronic heart failure outcomes as well as the consequences of their combination in an individual patient is unknown. Therefore, we sought to determine the incidence of isolated and multiple CHIP-mutations in a larger cohort of patients with chronic heart failure and their association with mortality.